Dental caries, a multifactorial complex disease, remains the one of the most common chronic disease of human beings. The etiology of dental caries has been studied extensively, and both environmental and genetic factors have been implicated in caries risk. Our long-term goal is to improve understanding of the mechanism leading to dental caries development in both children and adults by uncovering underlying genetic risk factors that alone or through interaction with environmental factors, increase caries risk, thus informing new strategies for prevention and treatment. The objective of this application, which is the next step in pursuit of that goal, is to develop and test new approaches for modeling dental caries in genetic epidemiology studies, and then to apply those approaches to better understand the interaction between genetic and environmental risk factors using a large existing genome-wide dataset. In Aim 1 we will study epidemiological properties, heritabilities, and modeling strategies for various caries phenotypes, and in Aim 2 we will look at the power of different gene x environment modeling strategies in the context of whole-genome scanning. The successful completion of Aims 1 and 2 will provide critical statistical and epidemiological tools for current and future studies of the genetic epidemiology of dental caries. In Aim 3 we will apply the best approaches from Aims 1 and 2 to several existing GWAS caries datasets to identify and understand genetic and environmental risk factors that affect caries risk. The successful completion of Aim 3 will lead to new discoveries about the etiology of caries, and in particular about the gene x environment interactions that differentially affect risk in primary, permanent, and mixed dentition. This better understanding will eventually lead to better prevention and treatment. PUBLIC HEALTH RELEVANCE: Dental caries, a multifactorial complex disease, remains the one of the most common chronic diseases of human beings. We propose to compare and evaluate a variety of caries modeling strategies for identifying genetic and environmental risk factors and their interactions. The successful completion of this project will eventually lead to better understanding of the etiology, prevention and even the customized treatment strategies of caries.